Mosquitoes utilize a variety of strategies to combat pathogens, including viruses. The long term_ goal of the PIs research is to elucidate, at the molecular level, the immune responses of the mosquito vector Aedes aegypti to infection with a range of viral pathogens, including those that could be used as agents for bioterrorism. In recent years, dengue fever has emerged as one of the most serious vector borne viral diseases. The molecular biology of dengue virus propagation in the mosquito vector is largely unknown, but the genome sequence and reverse genetic and functional genomics tools that are now available provide a means of dissecting the mosquito's anti viral defense systems in greater detail. In this proposal, we will apply these tools to characterize the Ae. aegypti mosquito's innate immune defense against the dengue virus. We have already showed that the mosquito is employing the Toll and JAK STAT immune pathways to limit dengue virus infection. We will now expand on this finding and characterize the mosquito's broader molecular immune responses to virus infection at multiple time points and tissues in Specific Aim 1. We will analyze the implication of the mosquito's immune pathways in defense against dengue virus infection in a greater detail in Specific Aim 2. In addition to the basic knowledge generated by the proposed experiments, this project should also provide a variety of tools that can be used for the development of novel antiviral control strategies.